CN103341217A - Preparation method for film used for preventing postoperative tissue adhesion - Google Patents
Preparation method for film used for preventing postoperative tissue adhesion Download PDFInfo
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- CN103341217A CN103341217A CN2013102324354A CN201310232435A CN103341217A CN 103341217 A CN103341217 A CN 103341217A CN 2013102324354 A CN2013102324354 A CN 2013102324354A CN 201310232435 A CN201310232435 A CN 201310232435A CN 103341217 A CN103341217 A CN 103341217A
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- thin film
- polyethylene glycol
- glutamic acid
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Abstract
The invention provides a preparation method for a film used for preventing postoperative tissue adhesion. The preparation method comprises the following steps: mixing poly-L-glutamic acid with chitosan and polyethylene glycol; then drying a poly-L-glutamic acid/chitosan/polyethylene glycol solution at a temperature of 25 to 50 DEG C under vacuum or in flowing air so as to prepare a poly-L-glutamic acid/chitosan/polyethylene glycol semi-interpenetrating polymer network film; and carrying out flushing with deionized water and drying again so as to obtain the anti-adhesion film with stable properties. The material of the film capable of preventing postoperative tissue adhesion has the advantages of good biocompatibility, adjustability of degradation time, uniform thickness, elasticity, simple preparation technology, a wide range of application and great market potential and application values.
Description
Technical field
The invention belongs to the preparation field of medical supplies, particularly a kind of be used to preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards.
Background technology
Clinically, behind the surgical operation the bad adhesion irrelevant with tissue repair can appear.For example the intestinal adhesion after abdominal cavity operation incidence rate is up to 79～90%, and the damage tendon also sticks together after reparation easily, causes the tendon afunction.At present, being used for the method for Film with Preventing Adhesion has Drug therapy, Biotherapeutics and adopts Antiadhesive film etc.In these methods, the anti thin film is a kind of effective method.Existing Antiadhesive film is biological absorbable medical film, and polylactic acid membrane and hyaluronic acid membrane are arranged.
Polylactic acid-based anti thin film has good mechanical property, advantages such as biocompatibility and degradation property excellence, but topmost problem be become fragile easily after implanting inhomogeneous, no pliability, tractive, and may be because local acid accumulation causes inflammation.
Hyaluronic acid membrane is to use more and ripe material clinically.But natural hyaluronic acid is shorter in the implant site retention time, and its anti effect can not reach desirable effect.And hyaluronic acid belongs to animal sources more, has the immunogenicity problem in vivo, and it extracts and purge process complexity, causes patient's cost height of seeking medical advice.
So the problem that present medical anti-adhesive membrane technology also needs to solve has:
1) biocompatibility is relatively poor.The content of water is compared with the oil-soluble macromolecule up to 70% in the tissue, and water soluble polymer and tissue have better affinity.
2) degradation time is uncontrollable.Different wound site have different requirements for the degradation time of Antiadhesive film.For example: the abdomen gut surgery can restore in common 28 days, and the degradation time of Antiadhesive film should be at this more than time; After yet tendon is injured, needed for 3 weeks just began to carry out functional exercise, its degradation time inevitable requirement is longer.
3) pliability is poor.Wound surface generally is rough behind the surgical operation, and soft and anti thin film that certain intensity arranged is flap coverage better, thereby plays the effect of separating tissues.
Summary of the invention
The objective of the invention is to overcome the defective of existing anti thin film, provide a kind of be used to preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards.It is controlled to prepare a kind of degradation time, and biocompatibility is good, and thickness is even, but tractive, resilient medical anti-adhesive thin film.
For achieving the above object, the present invention adopts following technological means:
A kind of be used to preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards, may further comprise the steps:
1) L-glutamic acid is dissolved among rare NaOH, adds Polyethylene Glycol, be stirred to Polyethylene Glycol and dissolve fully; L-glutamic acid and chitosan by-COOH and-the NH2 mol ratio is the 1:1 proportioning, adds chitosan under the high-speed stirred, drips acetic acid and regulates pH to 4～5 and makes chitosan dissolve fully, forms polyelectrolyte complex compound with L-glutamic acid; After the stirring at normal temperature 5～10 hours, contained the polyelectrolyte complex compound solution of Polyethylene Glycol uniformly; Each composition weight percentage composition is in the polyelectrolyte complex compound solution: polyelectrolyte complex compound: solvent: Polyethylene Glycol=1%～2%:97%～98%:0.5%～1%;
2) with the polyelectrolyte complex compound solution coat of above-mentioned preparation on strippable carrier, then in 25～50 ℃, after the drying, peel off from release of carrier under vacuum or the moving air, obtain translucent L-glutamic acid/chitosan/Polyethylene Glycol semi-intercrossing network thin film; Solid content by control polyelectrolyte complex compound solution is controlled build between 20～200 μ m;
3) with L-glutamic acid/chitosan/Polyethylene Glycol thin film of making through deionized water rinsing 3～5 times; The thin film that washed is fixed, and after drying obtains smooth translucent thin film.
The viscosity-average molecular weight of above-mentioned L-glutamic acid is 30000～120000.
The viscosity-average molecular weight of above-mentioned chitosan is 40000～50000.
The viscosity-average molecular weight of above-mentioned Polyethylene Glycol is 3000～5000.
The fixing means of above-mentioned thin film is smooth the spreading out of thin film that flushing is good, places between two metals, glass or the resin materials.
Compared with prior art, the present invention has following outstanding substantive distinguishing features and advantage significantly:
The present invention forms polyelectrolyte complex compound by using the static complexing between water miscible L-glutamic acid and the chitosan.L-glutamic acid is the water-soluble poly aminoacid that a kind of and human body have fabulous biocompatibility, and its catabolite glutamic acid aminoacid that is a kind of needed by human.Chitosan is to be obtained through deacetylation by the chitin that nature extensively exists, and is that a kind of histocompatibility is good, in vivo the degradable biological material.Polyethylene Glycol also is a kind of utilization bio-medical material widely, and biocompatibility is good, has the cell adhesion of preventing effect.Be introduced into to polyelectrolyte complex compound, can form a kind of biofilm that prevents the cell adhesion effect with semi-intercrossing network.The semi-intercrossing network technology is chemically to realize a kind of new technique of polymer physics blend, can effectively improve polymer performance.Exist interaction and physical entanglement between Polyethylene Glycol and polyelectrolyte complex compound, make the peg molecule chain be present in the polyelectrolyte system with a kind of stable morphology.The degradation time of anti thin film can adapt to the demand at different human body position by the molecular weight of regulating L-glutamic acid and chitosan.
The specific embodiment
The present invention is described further below in conjunction with specific embodiment.
Embodiment 1:
1) configuration L-glutamic acid/chitosan/polyglycol solution
Take by weighing L-glutamic acid powder 0.03551g, place the 4mL deionized water, NaOH solution to the L-glutamic acid that drips 3M under the magnetic stirring apparatus high-speed stirred just dissolves.Take by weighing Polyethylene Glycol powder 0.02g and be dissolved in the poly-L-glutamic acid acid solution, treat that Polyethylene Glycol dissolves the back fully and adds chitosan powder 0.04649g.Dropwise drip spirit of vinegar, regulate pH to 4.6, stirring at normal temperature 5 hours obtains uniform L-glutamic acid/chitosan/Polyethylene Glycol polyelectrolyte complex compound solution;
2) preparation L-glutamic acid/chitosan/Polyethylene Glycol semi-intercrossing network thin film
4mL polyelectrolyte complex compound solution is poured in the politef mould of 5cm*5cm.After curtain coating is even, place the ventilation 48h of about 25 ℃ of room temperatures, obtain smooth translucent thin film.With the translucent thin film that makes with deionized water rinsing 3 times after, be fixed between two microscope slides, room temperature is dried in the shade and is obtained smooth translucent thin film.
Embodiment 2:
1) configuration L-glutamic acid/chitosan/polyglycol solution
Take by weighing L-glutamic acid powder 0.0716g, place the 10mL deionized water, NaOH solution to the L-glutamic acid that drips 3M under the magnetic stirring apparatus high-speed stirred just dissolves.Take by weighing Polyethylene Glycol powder 0.05g and be dissolved in the poly-L-glutamic acid acid solution, treat that Polyethylene Glycol dissolves the back fully and adds chitosan powder 0.0926g.Dropwise drip spirit of vinegar, regulate pH to 4.6, stirring at normal temperature 5 hours obtains uniform L-glutamic acid/chitosan/Polyethylene Glycol polyelectrolyte complex compound solution;
2) preparation L-glutamic acid/chitosan/Polyethylene Glycol semi-intercrossing network thin film
10mL polyelectrolyte complex compound solution is poured in the politef mould of 10cm*5cm.After curtain coating is even, place the ventilation 48h of about 25 ℃ of room temperatures, obtain smooth translucent thin film.With the translucent thin film that makes with deionized water rinsing 3 times after, be fixed between two microscope slides, room temperature is dried in the shade and is obtained smooth translucent thin film.
Embodiment 3:
1) configuration L-glutamic acid/chitosan/polyglycol solution
Take by weighing L-glutamic acid powder 0.0178g, place the 2mL deionized water, NaOH solution to the L-glutamic acid that drips 3M under the magnetic stirring apparatus high-speed stirred just dissolves.Take by weighing Polyethylene Glycol powder 0.01g and be dissolved in the poly-L-glutamic acid acid solution, treat that Polyethylene Glycol dissolves the back fully and adds chitosan powder 0.0232g.Dropwise drip spirit of vinegar, regulate pH to 4.6, stirring at normal temperature 5 hours obtains uniform L-glutamic acid/chitosan/Polyethylene Glycol polyelectrolyte complex compound solution;
2) preparation L-glutamic acid/chitosan/Polyethylene Glycol semi-intercrossing network thin film
2mL polyelectrolyte complex compound solution is poured in the politef mould of 2cm*3cm.After curtain coating is even, place the ventilation 48h of about 25 ℃ of room temperatures, obtain smooth translucent thin film.With the translucent thin film that makes with deionized water rinsing 3 times after, be fixed between two microscope slides, room temperature is dried in the shade and is obtained smooth translucent thin film.
Claims (5)
1. one kind is used for preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards, it is characterized in that, may further comprise the steps:
1) L-glutamic acid is dissolved among rare NaOH, adds Polyethylene Glycol, be stirred to Polyethylene Glycol and dissolve fully; L-glutamic acid and chitosan by-COOH and-NH
2Mol ratio is the 1:1 proportioning, adds chitosan under the high-speed stirred, drips acetic acid adjusting pH to 4～5 and makes chitosan dissolve fully, forms polyelectrolyte complex compound with L-glutamic acid; After the stirring at normal temperature 5～10 hours, contained the polyelectrolyte complex compound solution of Polyethylene Glycol uniformly; Each composition weight percentage composition is in the polyelectrolyte complex compound solution: polyelectrolyte complex compound: solvent: Polyethylene Glycol=1%～2%:97%～98%:0.5%～1%;
2) with the polyelectrolyte complex compound solution coat of above-mentioned preparation on strippable carrier, then in 25～50 ℃, after the drying, peel off from release of carrier under vacuum or the moving air, obtain translucent L-glutamic acid/chitosan/Polyethylene Glycol semi-intercrossing network thin film; Solid content by control polyelectrolyte complex compound solution is controlled build between 20～200 μ m;
3) with L-glutamic acid/chitosan/Polyethylene Glycol thin film of making through deionized water rinsing 3～5 times; The thin film that washed is fixed, and after drying obtains smooth translucent thin film.
2. according to claim 1 be used to preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards, it is characterized in that the viscosity-average molecular weight of described L-glutamic acid is 30000～120000.
3. according to claim 1 be used to preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards, it is characterized in that the viscosity-average molecular weight of described chitosan is 40000～50000.
4. according to claim 1 be used to preventing from performing the operation the preparation method of tissue adhesion's thin film afterwards, it is characterized in that the viscosity-average molecular weight of described Polyethylene Glycol is 3000～5000.
5. the preparation method of the thin film be used to the back tissue adhesion that prevents from performing the operation according to claim 1 is characterized in that, the fixing means of described thin film is will good smooth the spreading out of thin film of flushing, places between two metals, glass or the resin materials.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310232435.4A CN103341217B (en) | 2013-06-13 | 2013-06-13 | Preparation method for film used for preventing postoperative tissue adhesion |
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| CN201310232435.4A CN103341217B (en) | 2013-06-13 | 2013-06-13 | Preparation method for film used for preventing postoperative tissue adhesion |
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| CN103341217A true CN103341217A (en) | 2013-10-09 |
| CN103341217B CN103341217B (en) | 2015-05-06 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381479A (en) * | 2017-08-08 | 2019-02-26 | 于晓彤 | A kind of surgical operation anti-sticking flush fluid |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1157569A (en) * | 1994-07-19 | 1997-08-20 | 阿斯特拉公司 | Anti-adhesion agent |
| US20020071855A1 (en) * | 2000-07-28 | 2002-06-13 | Anika Therapeutics, Inc | Bioabsorbable composites of derivatized hyaluronic acid and other biodegradable, biocompatible polymers |
| CN1569024A (en) * | 2004-04-30 | 2005-01-26 | 天津大学 | Novel post-operation antiadhesive materials and its preparation method |
| EP2025354A1 (en) * | 2006-05-16 | 2009-02-18 | Keio University | Agent for preventing organ adhesion and method for preventing adhesion using the same |
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2013
- 2013-06-13 CN CN201310232435.4A patent/CN103341217B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1157569A (en) * | 1994-07-19 | 1997-08-20 | 阿斯特拉公司 | Anti-adhesion agent |
| US20020071855A1 (en) * | 2000-07-28 | 2002-06-13 | Anika Therapeutics, Inc | Bioabsorbable composites of derivatized hyaluronic acid and other biodegradable, biocompatible polymers |
| CN1569024A (en) * | 2004-04-30 | 2005-01-26 | 天津大学 | Novel post-operation antiadhesive materials and its preparation method |
| EP2025354A1 (en) * | 2006-05-16 | 2009-02-18 | Keio University | Agent for preventing organ adhesion and method for preventing adhesion using the same |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381479A (en) * | 2017-08-08 | 2019-02-26 | 于晓彤 | A kind of surgical operation anti-sticking flush fluid |
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| CN103341217B (en) | 2015-05-06 |
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